An approach to the synthesis of 7β‐amino estrogens

Abstract The synthesis of 7β‐amino‐1,3,5(10)‐estratriene‐3,17β‐diol (1) has been accomplished using a sequence of transformations proceeding through the 6α,7α‐epoxy‐1,3,5(10)‐estratriene‐3.17β‐diol dibenzyl ether (6). This latter compound is reduced by LiAlH4to give the 7α‐hydroxy compound 7, which, upon subsequent treatment with tosyl chloride (to give8), followed by reaction with NaN3, provided the 7β‐azido‐1,3,5(10)‐estratriene‐3,17β‐diol dibenzyl ether (9). Reduction of9with LiAlH4, followed by catalytic removal of the benzyl ethers, gave1. Attempts to obtain an epoxide from 1,3,5(10),6‐estratetraene‐2,3–17β‐triol tribenzyl ether (17) failed, and led to the isolation of the corresponding 6α,7α‐diol (19) and 6β,7α‐diol (20). A novel transformation,viz.subsequent treatment of either19or20with SOCl2and LiAlH4, selectively provided 1,3,5(10)‐estratriene‐2,3,7α,17β‐tetraol 2,3,17‐tribenzyl ether (21). Further treatment of21, as delineated for7, provided the required 7β‐amino‐1,3,5(10)‐estratriene‐2,3,17β‐triol (2).